Thursday 28 August 2014

A retrospective study on incidence of lameness in domestic animals

Research (Published online: 15-08-2014)
9. A retrospective study on incidence of lameness in domestic animals - A. Mohsina, M. M. S Zama, P. Tamilmahan, M.B.Gugjoo, K. Singh, A. Gopinathan, M. Gopi and K.Karthik
Veterinary World, 7(8): 601-604


   doi: 10.14202/vetworld.2014.601-604


A. Mohsina: Division of Veterinary Surgery, Indian Veterinary Research Institute, Izatnagar, Bareilly, 243 122, Uttar Pradesh, India;sowparnika777@gmail.com
M. M. S Zama: Division of Veterinary Surgery, Indian Veterinary Research Institute, Izatnagar, Bareilly, 243 122, Uttar Pradesh, India;mmszama@yahoo.com
P. Tamilmahan: Division of Veterinary Surgery, Indian Veterinary Research Institute, Izatnagar, Bareilly, 243 122, Uttar Pradesh, India;drtamilmahan.bison@gmail.com
M. B. Gugjoo: Division of Veterinary Surgery, Indian Veterinary Research Institute, Izatnagar, Bareilly, 243 122, Uttar Pradesh, India;mbgugjoo@gmail.com
K. Singh: Division of Veterinary Surgery, Indian Veterinary Research Institute, Izatnagar, Bareilly, 243 122, Uttar Pradesh, India;ksuppli@yahoo.co.in
A. Gopinathan: Division of Veterinary Surgery, Indian Veterinary Research Institute, Izatnagar, Bareilly, 243 122, Uttar Pradesh, India;aswathykiran77@gmail.com
M. Gopi: Division of Animal Nutrition, Indian Veterinary Research Institute, Izatnagar, Bareilly, 243 122, Uttar Pradesh, India;gopsgopi72@gmail.com
K. Karthik: Division of Bacteriology, Indian Veterinary Research Institute, Izatnagar, Bareilly, 243 122, Uttar Pradesh, India;karthik_2bvsc@yahoo.co.in

Received: 23-04-2014, Revised: 28-06-2014, Accepted: 05-07-2014, Published online: 15-08-2014

Corresponding author: A. Mohsina, email: sowparnika777@gmail.com, Cell: +91-9458587867
Abstract

Aim: To study the incidence of lameness among different species of animals presented to the Veterinary Polyclinic, Indian Veterinary Research Institute, Izatnagar.
Materials and Methods: Outpatient department (OPD) records for the period from January 2006 to December 2010 were referred and information was collected regarding number of lameness in different species, breeds, type of injury, limb affected, gender, age at onset, treatment offered, outcome and any reoccurrence. In this study, fractured cases were not included.
Results: The incidence of lameness among different species were recorded: canine (56%), equine (21%), caprine (7%), feline (3%), cattle (7%), buffalo (5.47%), sheep (0.6%), monkey (0.39%) and swine (0.19%). In dog, the different conditions were reported with hind quarter weakness recording 55% of lameness followed by right hind limb lameness (14.7%), left hind limb lameness (12.6%), left forelimb lameness (12%), hip dislocation (6.3%) and hip dysplasia (4.2%). In caprines, important causes of lameness were right forelimb lameness (23%), right hind limb lameness (12%), left forelimb lameness (12%), posterior paresis (9%), left shoulder dislocation (14%) and right shoulder dislocation (6%). In cattle, 34.28% of cases with right hind limb lameness, 28.5% cases were due to HQW, 14.28% had hip dysplasia, 8.57% suffered left hind limb lameness, 6% cases were recorded with obturator nerve paralysis and 8.57% cases suffered contracted tendon in calves. In buffaloes, cases reported were right carpal arthritis, foot rot and left hind limb lameness (14.28%) each, due to bilateral upward luxation of patella and due bilateral purulent wound in stifle (18%) each and hip dislocation (21.4%). In equines, lameness were reported with right hind limb affection (13%), left forelimb affection (11%), right forelimb affection (17%), 4% each due to disease of right shoulder, HQW and both forelimb affection, lateral dislocation of patella (3%), affection of both hind limbs (9%), 5.5%each due to tenosynovitis, arthritis and bone spavin, 7% due to laminitis of right hind and forelimbs and 4.5% due to quittor.
Conclusion: The results show that lameness in animals is significantly affected by species, breed, age and sex of the animal. In dogs and cats, HQW is the most common cause of lameness. Among dogs, Mongrel and GSD breeds most affected. Male animals of less than 1 year or above 6 years are affected more. Hip dislocation is found to be more in male GSD and Labrador dogs and bilateral hip dislocation in spitz breeds. Hip dysplasia is also found to be more in GSD breed. Incidence of rickets is more in spitz dogs below 5 months of age. In equine and caprine species, right forelimb lameness, and in cattle right hind limb lameness is more. Hip dislocation, upward luxation of patella and wound are the major lameness causes in buffaloes.
Keywords: domestic animals, incidence, lameness.
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Molecular detection of Toxoplasma gondii DNA in milk and risk factors analysis of seroprevalence in pregnant women at Sharkia, Egypt

8. Molecular detection of Toxoplasma gondii DNA in milk and risk factors analysis of seroprevalence in pregnant women at Sharkia, Egypt -Heba A. Ahmed, Saleh M. Shafik, Mahmoud E. M. Ali, Sanya T. Elghamry and Alshymaa A. Ahmed
Veterinary World, 7(8): 594-600


   doi: 10.14202/vetworld.2014.594-600

 
Heba A. Ahmed: Department of Zoonoses, Faculty of Veterinary Medicine, Zagazig University, 44511, Zagazig, Egypt; heba_ahmed@zu.edu.eg
Saleh M. Shafik: Food Hygiene Department, Animal Health Research Institute, Mansoura, Egypt; Saleh_Shafik@yahoo.com
Mahmoud E. M. Ali: Food Hygiene Department, Animal Health Research Institute, Mansoura, Egypt; dr_hashem59@yahoo.com
Sanya T. Elghamry: Food Hygiene Department, Animal Health Research Institute, Mansoura, Egypt; sanyaelghamry@yahoo.com
Alshymaa A. Ahmed: Clinical pathology Department, Faculty of Medicine, Zagazig University, Egypt; doaa_ahmed57@yahoo.com

Received: 10-05-2014, Revised: 26-06-2014, Accepted: 03-07-2014, Published online: 12-08-2014

Corresponding author: Heba A. Ahmed, email: heba_ahmed@zu.edu.eg
Abstract

Aim: Toxoplasmosis is one of the most important zoonotic parasitic diseases worldwide. Infection is not only acquired by contact with the definitive host, but also by ingestion of raw milk and milk products. The aim of the study was to detect T. gondii DNA in milk samples, and to estimate anti-T. gondii antibodies in pregnant women for the analysis of the associated risk factors.
Materials and Methods: The study involved molecular examination of 150 milk samples collected from rural settings at Sharkia, Egypt. Seroprevalence of anti-T. gondii antibodies was determined in 100 pregnant women by indirect haemagglutination test. The analysis of risk factors associated with seropositive results was assessed by univariate and multivariate logistic regression.
Results: T. gondii DNA was detected in 8% and 2% of goat and sheep milk samples, respectively, while none of cow milk samples were positive. Seroprevalence of T. gondii antibodies in pregnant women was 82%, anti-T. gondii-IgG and anti-T. gondii-IgM were detected in 63% and 11% serum samples, respectively. The results showed a significant correlation between the seroprevalence and the contact with cats and consumption of raw milk and homemade cheese.
Conclusion: The role of raw milk in transmission of T. gondii cannot be excluded. Contact with cats remains the main risk factor for acquiring T. gondii infection; also consumption of raw milk and milk products is considered an important risk factor. Further large scale studies are recommended to clarify the association of T. gondii seroprevalence with different risk factors.
Keywords: B1 gene, pregnant women, raw milk, risk factors, seroprevalence, T. gondii.
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Detection of Mycobacterium avium subsp. paratuberculosis from cattle and buffaloes in Egypt using traditional culture, serological and molecular based methods

7. Detection of Mycobacterium avium subsp. paratuberculosis from cattle and buffaloes in Egypt using traditional culture, serological and molecular based methods - G. S. Abdellrazeq, M. M. El-Naggar, S. A. Khaliel and A. E. Gamal-Eldin
Veterinary World, 7(8): 586-593


   doi: 10.14202/vetworld.2014.586-593

 
G. S. Abdellrazeq: Department of Microbiology, Faculty of Veterinary Medicine, Alexandria University, Edfina, Rosetta-line, P. O. Box: 22758, Egypt;gaber.abdellatif@alexu.edu.eg
M. M. El-Naggar: Department of Microbiology, Faculty of Veterinary Medicine, Alexandria University, Edfina, Rosetta-line, P. O. Box: 22758, Egypt; mahmoud.elnaggar@alexu.edu.eg
S. A. Khaliel: Department of Microbiology, Faculty of Veterinary Medicine, Alexandria University, Edfina, Rosetta-line, P. O. Box: 22758, Egypt;khaliel1@yahoo.com
A. E. Gamal-Eldin: Department of Microbiology, Faculty of Veterinary Medicine, Alexandria University, Edfina, Rosetta-line, P. O. Box: 22758, Egypt;dr_asmaa9518@yahoo.com

Received: 03-05-2014, Revised: 02-07-2014, Accepted: 10-07-2014, Published online: 11-08-2014

Corresponding author: Gaber Abdellrazeq, email: gaber.abdellatif@alexu.edu.eg
Abstract

Background: Johne's disease (JD) caused by Mycobacterium avium subsp. paratuberculosis (MAP) represents a real threat to the agriculture and dairy food industries and believed to be a potential public health problem. Signs of infection in ruminant include weight loss, diarrhea, decreased milk production, and eventually death. The definition of an infected animal based either on the presence of anti-MAP antibodies, or positive bacterial culture. No treatment for the disease exists and controlling the disease is difficult due to its long latent period. JD is a worldwide problem and multiple studies in many countries have been carried out to determine the prevalence of MAP infections. Although some primary non intensive studies confirm presence of JD in Egypt, the disease is currently neglected by the official Egyptian veterinary agencies. There is no official data, no national control program, and no used vaccine.
Aim: This study aimed to evaluate three conventional diagnostic methods for MAP under the Egyptian circumstances with a general aim to determine the appropriate strategy to develop a JD control program. These methods were pooled fecal culture, humoral response and insertion sequence IS900 targets polymerase chain reaction (IS900 PCR).
Materials and Methods: Fecal and serum samples (500 each) were collected from Holstein-Friesian cattle and buffaloes housed in five Egyptian governorates. Fecal samples were examined for MAP on the basis of a strategic pooling procedure and performed on Herrold's Egg Yolk Agar Medium (HEYM). Smears were prepared from developed colonies and stained using a Ziehl-Neelsen (ZN) technique. The identity of developed colonies was further confirmed by PCR analysis of IS900 sequence. Sera from both culture-positive and culture-negative animals were evaluated individually for humoral response.
Results: Out of 50 pooled specimens, 34 (68%) fecal cultures were positive for MAP. Serum positive samples of culture-positive animals were 63/340 (18.5%). No serum positive were detected in the samples from culture-negative animals. DNA extractions from colonies of 34 culture-positive pooled samples were tested with the PCR targeted to IS900 and revealed 18 isolates (52.94%) were positive.
Conclusion: The present study has succeeded in isolating and identifying of MAP from Egyptian cattle and buffaloes in five governorates. The results confirm the epizoology of JD in Egypt and encourage the decision-makers to start creating a program to control it. Pooling procedure for MAP culture is an efficient and reliable method. However, the findings suggest the importance of using both ELISA and fecal culture in MAP diagnosis and control.
Keywords: culture, ELISA, IS900 PCR, Johne's disease, Mycobacterium avium subsp. paratuberculosis.
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Three-quarters of depressed cancer patients do not receive treatment for depression; new approach could transform care

Three papers published in The Lancet Psychiatry, The Lancet, and The Lancet Oncology reveal that around three-quarters of cancer patients who have major depression are not currently receiving treatment for depression, and that a new integrated treatment program is strikingly more effective at reducing depression and improving quality of life than current care.
An analysis of data from more than 21,000 patients attending cancer clinics in Scotland, UK, published inThe Lancet Psychiatry, found that major depression is substantially more common in cancer patients than in the general population. Major depression was most common in patients with lung cancer (13%) and lowest in those with genitourinary cancer (6%). Moreover, nearly three quarters (73%) of depressed cancer patients were not receiving treatment.
To address the problem of inadequate treatment the SMaRT Oncology-2 randomised trial, published inThe Lancet, evaluated the effectiveness of a new treatment program called 'Depression Care for People with Cancer' (DCPC). DCPC is delivered by a team of specially trained cancer nurses and psychiatrists, working in collaboration with the patient's cancer team and general practitioner, and is given as part of cancer care. It is a systematic treatment program that includes both antidepressants and psychological therapy.
The trial, involving 500 adults with major depression and a cancer with a good prognosis (predicted survival more than 12 months) compared DCPC with usual care [1]. DCPC was strikingly more effective at reducing depression. At 6 months, 62% of the patients who received DCPC responded to treatment (at least a 50% reduction in the severity of their depression) compared with only 17% of those who received usual care. This benefit was sustained at 12 months. DCPC also improved anxiety, pain, fatigue, functioning, and overall quality of life. Moreover, the cost of providing DCPC was modest (£613 per patient) making it a cost-effective way to improve cancer patients' quality of life.
According to lead author Professor Michael Sharpe from the University of Oxford in the UK, "The huge benefit that DCPC delivers for patients with cancer and depression shows what we can achieve for patients if we take as much care with the treatment of their depression as we do with the treatment of their cancer."
To see if patients with a poor prognosis cancer could also benefit from this approach, the SMaRT Oncology-3 randomised trial, published in The Lancet Oncology, tested a version of DCPC adapted for patients with a typically poor prognosis cancer (lung cancer). The trial, involving 142 patients with lung cancer and major depression, found that those who received the lung cancer version of DCPC had a significantly greater improvement in depression than those who received usual care during 32 weeks of follow-up. The lung cancer-specific version of DCPC also improved anxiety, functioning, and quality of life.
According to study leader Dr Jane Walker from the University of Oxford and Sobell House Hospice in Oxford in the UK, "Patients with lung cancer often have a poor prognosis. If they also have major depression that can blight the time they have left to live. This trial shows that we can effectively treat depression in patients with poor prognosis cancers like lung cancer and really improve patients' lives."
Story Source:
The above story is based on materials provided by The Lancet. Note: Materials may be edited for content and length.
Journal References:
  1. Michael Sharpe et al. Prevalence, associations, and adequacy of treatment of major depression in patients with cancer: a cross-sectional analysis of routinely collected clinical data. The Lancet Psychiatry, August 2014 DOI:10.1016/S2215-0366(14)70313-X
  2. Michael Sharpe, Jane Walker, Christian Holm Hansen, Paul Martin, Stefan Symeonides, Charlie Gourley, Lucy Wall, David Weller, Gordon Murray. Integrated collaborative care for comorbid major depression in patients with cancer (SMaRT Oncology-2): a multicentre randomised controlled effectiveness trial.The Lancet, 2014; DOI: 10.1016/S0140-6736(14)61231-9
  3. Jane Walker, Christian Holm Hansen, Paul Martin, Stefan Symeonides, Charlie Gourley, Lucy Wall, David Weller, Gordon Murray, Michael Sharpe. Integrated collaborative care for major depression comorbid with a poor prognosis cancer (SMaRT Oncology-3): a multicentre randomised controlled trial in patients with lung cancer. The Lancet Oncology, 2014; DOI: 10.1016/S1470-2045(14)70343-2
Cite This Page:
The Lancet. "Three-quarters of depressed cancer patients do not receive treatment for depression; new approach could transform care." ScienceDaily. ScienceDaily, 27 August 2014. <www.sciencedaily.com/releases/2014/08/140827203635.htm>.
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A modified version of the Clostridium novyi (C. novyi-NT) bacterium can produce a strong and precisely targeted anti-tumor response in rats, dogs and now humans, according to a new report from Johns Hopkins Kimmel Cancer Center researchers.

A modified version of the Clostridium novyi (C. novyi-NT) bacterium can produce a strong and precisely targeted anti-tumor response in rats, dogs and now humans, according to a new report from Johns Hopkins Kimmel Cancer Center researchers.
In its natural form, C. novyi is found in the soil and, in certain cases, can cause tissue-damaging infection in cattle, sheep and humans. The microbe thrives only in oxygen-poor environments, which makes it a targeted means of destroying oxygen-starved cells in tumors that are difficult to treat with chemotherapy and radiation. The Johns Hopkins team removed one of the bacteria's toxin-producing genes to make it safer for therapeutic use.
For the study, the researchers tested direct-tumor injection of the C. novyi-NT spores in 16 pet dogs that were being treated for naturally occurring tumors. Six of the dogs had an anti-tumor response 21 days after their first treatment. Three of the six showed complete eradication of their tumors, and the length of the longest diameter of the tumor shrunk by at least 30 percent in the three other dogs.
Most of the dogs experienced side effects typical of a bacterial infection, such as fever and tumor abscesses and inflammation, according to a report on the work published online Aug. 13 in Science Translational Medicine.
In a Phase I clinical trial of C. novyi-NT spores conducted at MD Anderson Cancer Center, a patient with an advanced soft tissue tumor in the abdomen received the spore injection directly into a metastatic tumor in her arm. The treatment significantly reduced the tumor in and around the bone. "She had a very vigorous inflammatory response and abscess formation," according to Nicholas Roberts, Vet.M.B., Ph.D. "But at the moment, we haven't treated enough people to be sure if the spectrum of responses that we see in dogs will truly recapitulate what we see in people."
"One advantage of using bacteria to treat cancer is that you can modify these bacteria relatively easily, to equip them with other therapeutic agents, or make them less toxic as we have done here, " said Shibin Zhou, M.D., Ph.D., associate professor of oncology at the Cancer Center. Zhou is also the director of experimental therapeutics at the Kimmel Cancer Center's Ludwig Center for Cancer Genetics and Therapeutics. He and colleagues at Johns Hopkins began exploring C. novyi's cancer-fighting potential more than a decade ago after studying hundred-year old accounts of an early immunotherapy called Coley toxins, which grew out of the observation that some cancer patients who contracted serious bacterial infections showed cancer remission.
The researchers focused on soft tissue tumors because "these tumors are often locally advanced, and they have spread into normal tissue," said Roberts, a Ludwig Center and Department of Pathology researcher. The bacteria cannot germinate in normal tissues and will only attack the oxygen-starved or hypoxic cells in the tumor and spare healthy tissue around the cancer.
Verena Staedtke, M.D., Ph.D., a Johns Hopkins neuro-oncology fellow, first tested the spore injection in rats with implanted brain tumors called gliomas. Microscopic evaluation of the tumors showed that the treatment killed tumor cells but spared healthy cells just a few micrometers away. The treatment also prolonged the rats' survival, with treated rats surviving an average of 33 days after the tumor was implanted, compared with an average of 18 days in rats that did not receive the C. noyvi-NT spore injection.
The researchers then extended their tests of the injection to dogs. "One of the reasons that we treated dogs with C. novyi-NT before people is because dogs can be a good guide to what may happen in people," Roberts said. The dog tumors share many genetic similarities with human tumors, he explained, and their tumors appeared spontaneously as they would in humans. Dogs are also treated with many of the same cancer drugs as humans and respond similarly.
The dogs showed a variety of anti-tumor responses and inflammatory side effects.
Zhou said that study of the C. novyi-NT spore injection in humans is ongoing, but the final results of their treatment are not yet available. "We expect that some patients will have a stronger response than others, but that's true of other therapies as well. Now, we want to know how well the patients can tolerate this kind of therapy."
It may be possible to combine traditional treatments like chemotherapy with the C. novyi-NT therapy, said Zhou, who added that the researchers have already studied these combinations in mice.
"Some of these traditional therapies are able to increase the hypoxic region in a tumor and would make the bacterial infection more potent and increase its anti-tumor efficiency," Staedtke suggested. "C. novyi-NT is an agent that could be combined with a multitude of chemotherapy agents or radiation."
"Another good thing about using bacteria as a therapeutic agent is that once they're infecting the tumor, they can induce a strong immune response against tumor cells themselves," Zhou said.
Previous studies in mice, he noted, suggest that C. novyi-NT may help create a lingering immune response that fights metastatic tumors long after the initial bacterial treatment, but this effect remains to be seen in the dog and human studies.
Story Source:
The above story is based on materials provided by Johns Hopkins Medicine. Note: Materials may be edited for content and length.
Journal Reference:
  1. N. J. Roberts, L. Zhang, F. Janku, A. Collins, R.-Y. Bai, V. Staedtke, A. W. Rusk, D. Tung, M. Miller, J. Roix, K. V. Khanna, R. Murthy, R. S. Benjamin, T. Helgason, A. D. Szvalb, J. E. Bird, S. Roy-Chowdhuri, H. H. Zhang, Y. Qiao, B. Karim, J. McDaniel, A. Elpiner, A. Sahora, J. Lachowicz, B. Phillips, A. Turner, M. K. Klein, G. Post, L. A. Diaz, G. J. Riggins, N. Papadopoulos, K. W. Kinzler, B. Vogelstein, C. Bettegowda, D. L. Huso, M. Varterasian, S. Saha, S. Zhou. Intratumoral injection of Clostridium novyi-NT spores induces antitumor responses.Science Translational Medicine, 2014; 6 (249): 249ra111 DOI:10.1126/scitranslmed.3008982
Cite This Page:
Johns Hopkins Medicine. "Injected bacteria shrink tumors in rats, dogs and humans." ScienceDaily. ScienceDaily, 13 August 2014. <www.sciencedaily.com/releases/2014/08/140813173906.htm>.
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Wednesday 27 August 2014

Study from the University of Liverpool has recommended investing in dog owner education and facilities as a strategy to target physical inactivity and problems such as obesity in both people and their pets.

A study from the University of Liverpool has recommended investing in dog owner education and facilities as a strategy to target physical inactivity and problems such as obesity in both people and their pets.
In a review of scientific papers published since 1990, the researchers found that access to dog-friendly walking environments and better education about dogs' physical needs, could all motivate people to get out and take more exercise with their pets.
It is estimated that 40% of dog owners don't take their dogs for a walk. In the UK, almost a quarter of households own a dog, but less than half of adults meet the recommended level of 150 minutes a week of physical activity.
To find out how to motivate people to use dog walking as a form of exercise, the researchers from the University's Institute of Infection and Global Health reviewed 31 research studies from the UK, USA, Australia and Japan.
Among the most common findings was that dog owners have a varied understanding of how much exercise their dog needs. This affected how much they took their dog for a walk and this is something that could be addressed with education programs.
Similarly, people without access to high quality local areas that support dog walking, for example parks where dogs are allowed off-leash and poo-disposal facilities are provided, were less likely to walk with their dog and missed out on the associated health benefits.
Population health scientist, Dr Carri Westgarth led the study. She said: "It is easy to assume that people who own dogs are more likely to take exercise, but the reality can be very different. If all people who owned a dog walked with it every day, physical activity levels would be much improved, benefiting the health of both the owners and their canine companions.
"There are a large number of reasons why people do or don't walk their dog and it is worth considering how we can address this when designing strategies for reducing obesity, or when planning urban areas and public open space. Not being able to let their dog off the leash is a particular put-off."
The most striking but understandable finding was that the strength of the dog-owner bond is important -- owners who were highly attached to their dogs and felt that their dogs gave them support were more likely to walk with it.
Dr Westgarth said: "The study also found that some people are worried about their dogs' behaviour and may be less likely to take it out to the park -- potentially out of embarrassment or worry about how it might act -- but lack of walks may also be causing this bad behaviour, due to boredom, frustration or lack of socialisation.
"There aren't many studies in this area at the moment, but with such a large proportion of people having a dog, it seems that better education, facilities and improved relationships with our pets could be a great way for a large portion of the population to feel encouraged to exercise."
Story Source:
The above story is based on materials provided by University of Liverpool. Note: Materials may be edited for content and length.
Journal Reference:
  1. Carri Westgarth, Robert M Christley, Hayley E Christian. How might we increase physical activity through dog walking?: A comprehensive review of dog walking correlates. International Journal of Behavioral Nutrition and Physical Activity, 2014; 11 (1): 83 DOI: 10.1186/1479-5868-11-83
Cite This Page:
University of Liverpool. "Education, dog-friendly neighborhoods could tackle obesity." ScienceDaily. ScienceDaily, 26 August 2014. <www.sciencedaily.com/releases/2014/08/140826100849.htm>.
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Vaccine researchers have developed a strategy aimed at generating broadly cross-reactive antibodies against the influenza virus: embrace the unfamiliar.

Vaccine researchers have developed a strategy aimed at generating broadly cross-reactive antibodies against the influenza virus: embrace the unfamiliar.
In recent years, researchers interested in a "universal flu vaccine" identified a region of the viral hemagglutinin protein called the stem or stalk, which doesn't mutate and change as much as other regions and could be the basis for a vaccine that is protective against a variety of flu strains.
In an Emory Vaccine Center study, human volunteers immunized against the avian flu virus H5N1 readily developed antibodies against the stem region of the viral hemagglutinin protein. In contrast, those immunized with standard seasonal trivalent vaccines did not, instead developing most of their antibodies against the more variable head region. H5N1, regarded as a potential pandemic strain, is not currently circulating in the United States and the volunteers had not been exposed to it before.
The results are scheduled for publication in Proceedings of the National Academy of Sciences.
The key to having volunteers' bodies produce antibodies against the stem region seemed to be their immune systems' unfamiliarity with the H5N1 type of virus, says lead author Ali Ellebedy, PhD, postdoctoral fellow in the laboratory of Rafi Ahmed, PhD, director of Emory Vaccine Center.
Collaborators at University of Chicago and Mount Sinai School of Medicine contributed to the study.
"Our previous research led us to hypothesize that immune responses to the stem region are likely to be stronger after exposure to hemagglutinin molecules derived from flu viruses which the human population has been minimally exposed to," Ellebedy says.
Emory Vaccine Center researchers had found that several patients infected with the 2009 H1N1 pandemic flu strain developed broadly cross-reactive antiviral antibodies. In 2009, most younger adults had never been exposed to the H1N1 pandemic strain and thus had no immune cells producing antibodies against it.
But later, after that H1N1 strain started circulating widely in the population, it became part of the standard seasonal trivalent vaccine. When volunteers' immune responses to the seasonal vaccine were analyzed, most of the antibodies they generated reacted to the head region of hemagglutinin.
Immune cells that produce antibodies against the stem region are widely prevalent in humans, but at low levels, the team found. But the standard trivalent seasonal vaccine tends not to amplify them. This led the team to ask whether vaccination with something different enough, such as H5N1, would stimulate production of "anti-stem" antibodies.
"We had already performed a big H5N1 study back in 2008, so we went back and tested our hypothesis with some novel reagents that allowed us to dissect responses that are directed to the head vs. the stem regions," Ellebedy says.
The team analyzed levels of antibody directed against different parts of the hemagglutinin protein in 17 volunteers, before and after H5N1 vaccination. Anti-stem antibody levels rose an average of four-fold after the first H5N1 vaccination. After a booster shot, however, anti-head responses dominated while anti-stem responses were feeble.
The authors conclude:
"Our data indicate that most humans are capable of establishing a humoral immune memory that is specific to the conserved HA stem region…Overall, our data raise the important question of what would be the minimal 'concentration' of antistem antibodies required to provide in vivo protection. Therefore, it will be important in future studies to determine the quantity of HA stem-specific antibodies or memory B cells that would positively correlate with better clinical outcomes against influenza infections."
"Our findings delineate a potential vaccination strategy where H5N1 or H7N9 immunization could be used not only for immunologically priming the population to quickly respond to serious pandemic influenza threats, but also for generating broadly neutralizing antibodies against influenza in humans."
Story Source:
The above story is based on materials provided by Emory Health Sciences. Note: Materials may be edited for content and length.
Journal Reference:
  1. Ali H. Ellebedy, Florian Krammer, Gui-Mei Li, Matthew S. Miller, Christopher Chiu, Jens Wrammert, Cathy Y. Chang, Carl W. Davis, Megan Mccausland, Rivka Elbein, Srilatha Edupuganti, Paul Spearman, Sarah F. Andrews, Patrick C. Wilson, Adolfo García-Sastre, Mark J. Mulligan, Aneesh K. Mehta, Peter Palese, and Rafi Ahmed. Induction of broadly cross-reactive antibody responses to the influenza HA stem region following H5N1 vaccination in humans. PNAS, August 2014 DOI: 10.1073/pnas.1414070111
Cite This Page:
Emory Health Sciences. "Key to universal flu vaccine: Embrace the unfamiliar." ScienceDaily. ScienceDaily, 25 August 2014. <www.sciencedaily.com/releases/2014/08/140825152554.htm>.
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